If you’re a dog lover, we have some good news. It turns out that a better understanding of the mechanisms behind aging and cancer could reduce the number of canines over the age of 10 that die from cancer each year. A better understanding of those same mechanisms may even yield big news for humans down the road.
Recently, University of Minnesota researchers made a surprising discovery about one gene implicated in aging.
And it all centered around a gene known as the telomerase (TOO-low-mears) reverse transcriptase gene, or “TERT.” The protein is part of a complex, “telomerase”, that was previously thought to be responsible for differing cancer risks between dog breeds.
But when Camille McAloney, a dual-degree D.V.M./Ph.D. student, investigated TERT in the University of Minnesota’s Modiano Lab alongside Kevin Silverstein, Ph.D., of the Minnesota Supercomputing Institute; Jaime Modiano, V.M.D., Ph.D., professor in the College of Veterinary Medicine and Masonic Cancer Center member; and Anindya Bagchi, Ph.D., she found otherwise.
“We found there is virtually no correlation in TERT genetic differences between the dog breeds we studied,” said McAloney. “That implies the TERT gene is less responsible for cancer risk than previously thought.”
In the four dog breeds McAloney studied – some very prone to cancer, others not – there wasn’t a significant difference in this one gene thought to be key to cancer risk.
While the Shih Tzus, Dachshunds, Irish Wolfhounds, and Newfoundlands in the study were different in many respects, any changes or mutations to TERT weren’t segregated by dog size or breed. That means no breed-specific polymorphisms, or genetic variations, have occurred in TERT since dog breeds were first established.
Any changes to TERT would have occurred in the domesticated dog’s wild predecessor: the wolf. And a gene barely changed since different dog breeds first emerged is unlikely to be responsible for such major variations in cancer risk from one dog breed to another today.
“Even more interesting than gene mutations not being affected by breeding,” said Anindya Bagchi, Ph.D., assistant professor with the U of M Masonic Cancer Center and Department of Genetics, Cell Biology and Development, “is that many of the mutations discovered were heterozygous.”
But let’s take a step back. If the TERT gene doesn’t equate to canine cancer, there’s another hypothesis.
There are two types of changes that can occur in genes: heterozygous and homozygous. (Remember Punnett Squares from science class?) We have two copies of each gene, but heterozygous changes, or mutations, occur in just one of those two. Homozygous mutations occur in both.
If not a single dog studied by McAloney had the homozygous mutation of the TERT gene that means this kind of genetic change likely isn’t tolerated. A dog that inherited two copies of the TERT mutation would die.
That’s the part Bagchi calls interesting because it leads to the question of why wolves underwent the original genetic mutation leading to only heterozygous mutations today. What was the health benefit?
The answer could lead to a better understanding of canine and human cancer alike.